@article{83b19e55800a4fb68625543099e7f731,
title = "Predicting clinical decline and conversion to Alzheimer{\textquoteright}s disease or dementia using novel Elecsys Aβ(1–42), pTau and tTau CSF immunoassays",
abstract = "We evaluated the performance of CSF biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients with cognitive symptoms. CSF samples from patients in two multicentre longitudinal studies (ADNI, n = 619; BioFINDER, n = 431) were analysed. Aβ(1–42), tTau and pTau CSF concentrations were measured using Elecsys CSF immunoassays, and tTau/Aβ(1–42) and pTau/Aβ(1–42) ratios calculated. Patients were classified as biomarker (BM)-positive or BM-negative at baseline. Ability of biomarkers to predict risk of clinical decline and conversion to AD/dementia was assessed using pre-established cut-offs for Aβ(1–42) and ratios; tTau and pTau cut-offs were determined. BM-positive patients showed greater clinical decline than BM-negative patients, demonstrated by greater decreases in MMSE scores (all biomarkers: –2.10 to –0.70). Risk of conversion to AD/dementia was higher in BM-positive patients (HR: 1.67 to 11.48). Performance of Tau/Aβ(1–42) ratios was superior to single biomarkers, and consistent even when using cut-offs derived in a different cohort. Optimal pTau and tTau cut-offs were approximately 27 pg/mL and 300 pg/mL in both BioFINDER and ADNI. Elecsys pTau/Aβ(1–42) and tTau/Aβ(1–42) are robust biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients, and may support AD diagnosis in clinical practice.",
author = "Kaj Blennow and Shaw, {Leslie M.} and Erik Stomrud and Niklas Mattsson and Toledo, {Jon B.} and Katharina Buck and Simone Wahl and Udo Eichenlaub and Valeria Lifke and Maryline Simon and Trojanowski, {John Q.} and Oskar Hansson",
note = "Funding Information: K.B. served as a consultant or at advisory boards for Alzheon, BioArctic, Roche Diagnostics, Eli Lilly, Fujirebio Europe, Merck, Novartis and IBL International. His research team has received funds for research from Roche Diagnostics. He is the co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. L.M.S. received research support from NIH/NIA, ADNI (AG024904) and UPenn ADCC Biomarker Core (AG010124), MJFox Foundation for PD research, Roche, Lilly; provides QC oversight for Roche Elecsys CSF AD biomarker immunoassays for ADNI; and is a consultant for Roche, Lilly, Novartis. E.S., N.M., J.B.T. and J.Q.T. declare that they have no conflict of interest. S.W., U.E., V.L., M.S., and K.Bu. are Roche employees. O.H. acquired research support (for the institution) from Roche, GE Healthcare, Biogen, AVID Radiopharmaceuticals, Fujirebio and Euroimmun. In the past 2 years, he has received consultancy/speaker fees (paid to the institution) from Lilly, Roche and Fujirebio. Funding Information: This work has been developed by the authors on behalf of the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) and BioFINDER study. Data used in preparation of this article were obtained from the ADNI database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_ Acknowledgement_List.pdf. Data collection and sharing for this project were funded by ADNI (National Institutes of Health Grant U01 AG024904, Michael Weiner, PI) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institute of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organisation is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Penn AD Center (P30 AG010124) also provided support and the contribution of samples to ADNI. The BioFINDER study was supported by grants from the European Research Council, the Swedish Research Council, the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson{\textquoteright}s disease) at Lund University, the Crafoord Foundation, the Swedish Brain Foundation, the Knut and Alice Wallenberg foundation, the Marianne and Marcus Wallenberg foundation, the Sk{\aa}ne University Hospital Foundation, the Swedish Alzheimer Association, and the Swedish federal government under the ALF agreement. A complete list of BioFINDER members can be found at http://biofinder. se/the_biofinder_study_group/. The authors would like to thank Mehmet Can Mert and R{\"u}diger Laubender for providing statistical analysis support. Third-party medical writing assistance, under the direction of the authors, was provided by Louise Kelly, BSc, of Gardiner-Caldwell Communications, and was funded by Roche Diagnostics. COBAS, COBAS E and ELECSYS are trademarks of Roche. The presented analyses (design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review and approval of the manuscript; and decision to submit the manuscript for publication) were sponsored by Roche Diagnostics. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-54204-z",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
publisher = "Nature Publishing Group",
number = "1",
}